?DESCRIPTION (provided by applicant): Support is requested to continue a program designed to advance understanding of molecular mechanisms of vascular disease and to promote development of new diagnostic, therapeutic, and preventive strategies through the collaborative efforts of a group of experienced scientists focused on the unifying theme of cell adhesion. This group of scientists, with a history of productive collaborative interactions, will cooperate in studies directed at the unifying theme. To understand the regulation of platelet, endothelial cell, and leukocyte adhesion, we propose studies ranging from analysis of protein structure at atomic level of detail through biochemistry, cell biology, ex-vivo studies to analyze the effects of blood flow on adhesion and signaling, nanoscale resolution of integrin conformational changes and adaptor recruitment in live rolling neutrophls, and analysis of genetically-modified mice and zebrafish.